Ia/DR antigen-bearing cells play a decisive role in the presentation of antigen to syngeneic T-cells. Studies in this laboratory have demonstrated that Ia/DR expression by monocytes/macrophages can be induced by the cytokines IFN- Gamma and IFN Alpha and be suppressed by stimulants of a cAMP-mediated pathway such as PGE2. The state of monocyte/macrophage Ia/DR expression varies with the developmental, environmental and pathological state of the individual. We have demonstrated a low level of Ia/DR expression on monocytes/macrophages from subjects with reduced immune reactivity, including human newborns, SLE patients with defective lymphokine production, and anergic patients with far advanced Hodgkin's disease. Ia/DR antigens are expressed both on the surface of cells and shed from these cells, apparently on lipid vesicles. We have demonstrated significant Ia/DR shedding from human peripheral blood monocytes, a human monocytic cell line, and several EBV+ B-cell lines, but not from E-rosette forming T-cells. Exposure of peripheral blood adherent cells to human recombinant IFN-Gamma enhances the expression of DR antigens and subsequent shedding of this material. The role of shed DR material in in vitro immunological reactions is being evaluated. Preliminary results suggest that vesicular DR can activate allogeneic lymphocytes to produce interleukin 2.